Abstract Asthma incidence is increasing and warrants investigation of distinct immune mechanisms. Innate, non- antigen-dependent immunity has been shown to play a role in allergic responses. Our data suggest that the innate immune collectin, surfactant (SP-)-D, can function as an endogenous, anti-inflammatory regulator of allergic responses. We analyze T cell and SP-D interactions, and focus on T helper (Th) 17 T cells. Also, we investigate evidence that cytotoxic t-lymphocyte antigen 4 (CTLA4), an inhibitor of T cells, mediates SP-D effects. Our data indicate that SP-D diminishes IL-17 responses while increasing CTLA4. Our overall hypothesis is that SP-D is an endogenous regulator of immunity that decreases allergic inflammation by inducing immunosuppressive pathways within T cells. Aim 1 will investigate the mechanisms of SP-D modulation of T cell subsets. Aim 2 will analyze the biochemical and cellular mechanisms of SP-D binding to T cells. Aim 3 will focus on SP-D-dependent molecular mechanisms regulating CTLA4 expression. Aim 4 will investigate the response of T cell subsets to SP-D in cells obtained from asthmatic subjects. An anti-inflammatory role for SP-D, specifically in T cell activation, reveals a distinct pathway for potential therapeutic intervention in T cell mediated disorders. This proposal will examine biochemical and biological pathways that may lead to the development of candidates for therapeutic intervention for asthma.